4.7 Article

DRE-1/FBXO11-Dependent Degradation of BLMP-1/BLIMP-1 Governs C. elegans Developmental Timing and Maturation

期刊

DEVELOPMENTAL CELL
卷 28, 期 6, 页码 697-710

出版社

CELL PRESS
DOI: 10.1016/j.devcel.2014.01.028

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资金

  1. Deutsche Forschungsgemeinschaft [DFG/SFB635]
  2. Max Planck Society
  3. CECAD/DFG
  4. National Institutes of Health [R01-GM057587, R37-CA076584, R21-CA161108, R03 TW009040]

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Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions inanSCFE3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF (DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counter-parts. Taken together, posttranslational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes.

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